男男性行為者中透過性而獲得之腸道感染
資料來源：www.thelancet.com/infection Vol 23 June 2023
在刺胳針傳染病中，Katie Thorley 和同事廣泛描述了在英國同性戀、雙性戀和其他男男性行為者 (MSM)人群中出現超級耐藥 (XDR) 和多重耐藥志賀菌的 flexneri 2a血清型。 這文章遵循先前的幾篇在英國和其他高收入國家MSM 中發現耐多藥索尼氏志賀氏菌 (Shigella sonnei) 爆發流行之報告，以及在更廣泛背景下發生再浮現的其他腸道感染，例如A型肝炎病毒和性病淋巴肉芽腫，在全球相互關聯的 MSM 人群中。
在 MSM 和其他人群中，志賀氏桿菌已經獲得了多種抗生素類別之抗性突變，嚴重限制治療選擇。志賀氏菌屬可以很容易地從其他志賀氏菌屬和腸桿菌成員中獲得多重耐藥質粒。
Thorley 及其同事報告說，從 2021 年 9 月開始，成年男性個體（中位年齡 37 歲 [IQR 31-46]）中攜帶 blaCTX-M-27 的S flexneri痢疾桿菌病例持續增加（n=26），並且，有13個人中完成了患者問卷調查，其中10個人 (77%) 確定為男男性行為者。 S flexneri痢疾桿菌對頭孢曲鬆(Ceftriaxone) 的耐藥性是質粒介導的，由 blactx-m-27 基因編碼，並且與最近在包括在英國和澳大利亞 MSM 中出現的超級抗藥 blactx-m-27–窩藏於 S sonnei 痢疾桿菌案例同時發生。在英國的超級抗藥之 S sonnei 痢疾桿菌和 S flexneri 痢疾桿菌爆發中，據報導 Inc FII blactx-m-27 質粒結構非常相似。
因此，作者假設在社區中傳播的志賀氏菌屬的耐藥決定因素的水平轉移可能正在推動超級抗藥 之志賀氏菌屬的進一步傳播。該研究並沒有將英國的基因組數據與公開可用的全球基因組聯繫起來，也沒有比較來自英國和澳大利亞的志賀氏菌屬中的 blactx-m-27 質粒。然而，考慮到先前報導的洲際傳播MSM 中的耐藥志賀氏菌，有可能這些質粒高度相似。未來的工作應結合演化和全球視角，以更深入地了解驅動超級抗藥志賀氏菌之出現和傳播的因素。重要的是，對頭孢曲松耐藥的志賀氏菌屬的出現是一個極其令人擔憂的發展，因為在一些國家，非消化道給藥之頭孢曲松僅用於在口服喹諾酮類 (quinolones) 藥物因喹諾酮耐藥而失敗時需要住院的臨床嚴重病例身上。
出現胃腸道症狀的 MSM顯示出於感染原因，由於可能的病原體範圍廣泛、需根據病原體採取不同的治療方法，以及可能存在著耐藥性微生物，因此對醫療保健提供者形成了診斷和管理上的挑戰。對MSM 的鑑定要求臨床醫生詢問男性是否與男性發生過性行為，並且需患者無顧慮且願意向臨床醫生披露此信息。 臨床特徵有時可以為可能的腸溶性病原之線索。 例如，梨形鞭毛蟲 (Giardia lamblia) 引起的腸炎通常會導致噁心、腹部絞痛和水樣腹瀉，而帶血腹瀉可能顯示感染（例如，志賀氏菌屬Shigella spp、痢疾阿米巴原虫Entamoeba histolytica或性病淋巴肉芽腫 lymphogranuloma venereum）引起的結腸炎。但在實務中，僅對報告有胃腸道症狀的 MSM其可能的病原體診斷上通常很難充滿信心，除應單獨進行臨床表現檢視，並應檢測糞便樣本中適當範圍可能存在的病毒、細菌和寄生蟲病原體。並應確定 HIV 狀態，因為 HIV 感染者和低 CD4 細胞計數可能有伺機性腸道感染，例如隱孢子蟲 (ryptosporidium)。 有肛門直腸疼痛和分泌物提示可能是感染性直腸炎的個體應進行肛門拭子檢查淋病、衣原體、皰疹、梅毒和 mpox（以前稱為猴痘），無論有無肛門直腸病變肛門拭子測試均可能會有幫助涵蓋所有潛在的腸道和直腸病原體。如果透過 PCR 檢測到志賀氏菌屬，糞便培養和抗生素耐藥性檢測於指導治療和監測目的上會很重要。應以當地的 MSM 中已知的腸道病原體和抗生素耐藥性等流行病學資訊做為治療指導。
受到性行為的促進MSM 可能會爆發腸道病原體感染，例如直接口肛接觸和無症狀攜帶胃腸道病原體，基因組流行病學對腸道病原體爆發的分析，例如由Thorley 和同事所從事的，可以幫助追踪出現新的抗藥機制，定義那些處於危險中的人和傳播範圍，並將公共衛生介入措施集中送到最需要的地方。這項研究清醒地提醒人們迫切需要一個全面的和多學科的全球應對超級抗藥 (XDR) 志賀菌屬的傳播，包括研究和開發新的和改變用途的抗菌藥物，並加速發展疫苗。
我們聲明不存在競爭利益。在提交的工作之外， MYC 由國家健康與醫學研究理事會合作計畫撥款 app2003399 資助。在提交的工作之外， DAW 由國家健康和醫學研究資助委員會調查員撥款app1174555。
* Marcus Y Chen, Deborah A Williamson mchen@mshc.org.au
墨爾本性健康中心，阿爾弗雷德健康中心，墨爾本，VIC 3053，澳大利亞
（MYC）; 澳大利亞維多利亞州墨爾本莫納什大學醫學、護理和健康科學學院中央臨床學院 (MYC)； 澳大利亞維多利亞州墨爾本彼得·多爾蒂感染與免疫研究所墨爾本大學傳染病系 (DAW)； 澳大利亞維多利亞州墨爾本皇家墨爾本醫院維多利亞傳染病參考實驗室 (DAW)； 沃爾特和伊麗莎霍爾醫學研究所，墨爾本，澳大利亞維多利亞州 (DAW)
Sexually acquired enteric infections among men who have sex with men
www.thelancet.com/infection Vol 23 June 2023
In The Lancet Infectious Diseases, Katie Thorley and colleagues1 describe the emergence of extensively drug-resistant (XDR) and multidrug-resistant Shigella flexneri serotype 2a among gay, bisexual, and other men who have sex with men (MSM) in England. This Article follows several previous reports of outbreaks of multidrug-resistant Shigella sonnei among MSM in England and other high-income countries and occurs on a wider backdrop of the re-emergence of other enteric infections, such as hepatitis A virus and lymphogranuloma venereum, among interconnected populations of MSM globally.
Among MSM, and other populations, Shigella spp have acquired resistance mutations to multiple classes of antibiotics, severely limiting treatment options. Shigella spp can readily acquire multidrug resistance plasmids, both from other Shigella spp and from members of the Enterobacterales.5 Thorley and colleagues reported that,1 from September, 2021, there was a sustained increase in cases of S flexneri harbouring blaCTX-M-27 (n=26) among adult male individuals (median age 37 years [IQR 31–46]) and, of the 13 individuals who completed a patient questionnaire, ten (77%) identified as MSM. Ceftriaxone resistance in S flexneri was plasmid mediated, encoded by the blactx-m-27 gene, and was contemporaneous with the recent emergence of XDR blactx-m-27-harbouring S sonnei in MSM, including in England and Australia.2,6 Notably, in the XDR S sonnei and S flexneri outbreaks in England, the IncFII blactx-m-27 plasmid structure was reportedly very similar. As such, the authors hypothesise that horizontal transfer of resistance determinants in Shigella spp circulating in the community might be driving the further spread of XDR Shigella spp. The study did not contextualise genomic data in England with publicly available global S flexneri genomes, nor did it compare blactx-m-27 plasmids in Shigella spp from England and Australia.2,6 However, given the previously reported intercontinental dissemination of drug-resistant Shigella in MSM,3,7 it is plausible that these plasmids are highly similar. Future work should incorporate an evolutionary and global perspective to provide a deeper understanding of the factors driving the emergence and spread of XDR Shigella spp. Importantly, the appearance of Shigella spp resistant to ceftriaxone is an extremely worrying development, as parenteral ceftriaxone is, in some countries, reserved for clinically severe cases requiring hospital admission when oral quinolones have failed due to quinolone resistance.
MSM who present with gastrointestinal symptoms suggestive of an infectious cause present a diagnostic and management challenge for health-care providers because of the wide spectrum of possible pathogens, differing treatments depending on the pathogen, and the potential presence of antimicrobial-resistant organisms.2,8–10 Identification of MSM requires the clinician to ask men if they have had sex with men and that patients feel comfortable disclosing this information to the clinician. The clinical features can sometimes provide a clue as to the likely enteric pathogen. For example, enteritis due to Giardia lamblia typically causes nausea, abdominal cramps, and watery diarrhoea, whereas diarrhoea with blood could be indicative of colitis due to infections (eg, Shigella spp, Entamoeba histolytica, or lymphogranuloma venereum).8 However, in practice, it is usually difficult to be confident of the likely pathogen on the basis of clinical presentation alone, and testing of fecal samples for the appropriate range of possible viral, bacterial, and parasitic pathogens should be done in MSM reporting gastrointestinal symptoms. HIV status should be ascertained as individuals with HIV and a low CD4 cell count might have an opportunistic gut infection, such as Cryptosporidium. Individuals with anorectal pain and discharge suggestive of infectious proctitis should have anal swabs for gonorrhoea, chlamydia, herpes, syphilis, and mpox (formerly known as monkeypox), whether anorectal lesions are present or not. Multiplex PCR testing of fecal samples and anal swabs can be helpful in covering the full range of potential enteric and rectal pathogens. If Shigella spp are detected by PCR, fecal culture and antimicrobial resistance testing is important to guide therapy and for surveillance purposes. For more clinically severe cases of infectious diarrhoea in MSM, treatment might need to be initiated before the results of these investigations are known. Testing and treatment should be guided by the known epidemiology of enteric pathogens and antimicrobial resistance among MSM locally.
Outbreaks of enteric pathogens among MSM might be facilitated by sexual behaviours, such as direct oral–anal contact, and asymptomatic carriage of gastrointestinal pathogens. Genomic epidemiological analyses of outbreaks of enteric pathogens, as done by Thorley and collegues, can help to track the emergence of novel resistance mechanisms, define those at risk and the extent of transmission, and focus public health interventions to where they are most needed. The study is a sobering reminder of the urgent need for a comprehensive and multidisciplinary global response to the spread of XDR Shigella spp, including research and development into new and repurposed antimicrobials, and accelerated development of vaccines.
We declare no competing interests. MYC is funded by the National Health and Medical Research Council partnership project grant app2003399, outside of the submitted work. DAW is funded by the National Health and Medical Research Council investigator grant app1174555, outside of the submitted work.
*Marcus Y Chen, Deborah A Williamson mchen@mshc.org.au Melbourne Sexual Health Centre, Alfred Health, Melbourne, VIC 3053, Australia (MYC); Central Clinical School, Faculty of Medicine, Nursing, and Health Sciences, Monash University, Melbourne, VIC, Australia (MYC); Department of Infectious Diseases, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia (DAW); Victorian Infectious Diseases Reference Laboratory, Royal Melbourne Hospital, Melbourne, VIC, Australia (DAW); Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia (DAW)